This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Porphyria cutanea tarda (PCT) develops in some individuals who are predisposed by certain environmental and inherited susceptibility factors, and is manifested by skin photosensitivity and liver damage. Susceptibility factors include hepatitis C, alcohol use, smoking, iron overload, HIV, estrogens and an inherited partial deficiency of UROD. Why PCT develops in only a few individuals with these susceptibility factors, many of which are relatively common, is not known, and additional influences - most likely additional inherited differences - remain to be identified. We will investigate the novel hypothesis that genetic differences in enzymes that metabolize foreign chemicals may contribute to developing PCT. Aim 1. At least 120 patients with well documented PCT will be enrolled in a case-control study that will include two different groups of matched controls. DNA and lymphocytes will be isolated, and patients and controls studied for specific genetic differences in specific enzymes (e.g.CYP1A1, CYP1A2, CYP2E1, GSTM1 and GSTT1). Aim 2. Associations with clinical features, known susceptibility factors, treatment response and frequency of relapse will be examined using logistic regression models. Aim 3. DNA and lymphocytes from these patients and matched controls, and information regarding clinical features and known susceptibility factors will be stored as a resource for future studies of additional genetic susceptibility factors for PCT. Results will be summarized and analyzed statistically to compare the PCT group with the two control groups. This study and projects which follow will lead to a better understanding of PCT.